Epilepsy is the most common brain disorder worldwide with no age, racial, social class, national, or geographic boundaries. It affects 67 million people, 85% of whom live in developing countries. Refractory (uncontrolled) epilepsy and misdiagnosis are two major challenges in the field of epilepsy worldwide. Despite decades of research, new antiepileptic drugs (AEDs), and advances in surgical therapy, many patients suffer from uncontrollable epilepsy or the side effects of AEDs and surgical treatment. Furthermore, misdiagnosis of epilepsy is very common in patients of all ages. Misdiagnosis of epilepsy can lead to serious complications as seizures and antiepileptic drugs can cause cognitive impairments and behavioral problems. There is growing evidence that brain stimulation may be used as a potential therapy for refractory epilepsy. However, the therapeutic results of stimulation are not proven. Existing stimulation approaches demonstrate suboptimal effect or involve significant risks. Presently, the primary diagnostic tool for epilepsy is conventional electroencephalography (EEG) which suffers from poor sensitivity/specificity, a root cause of misdiagnosis because it leads to inaccurate spike and seizure detection and foci localization. To address these problems, our long-term research goals are, through multi-disciplinary collaboration between the U.S. and Mexico, to develop (1) a tripolar concentric ring electrode (TCRE) based noninvasive transcutaneous focal stimulation (TFS) neuromodulation system for epilepsy therapy, and (2) a TCRE EEG system to improve epilepsy diagnosis. Preliminary studies generated promising results, thus warrant further investigation. The proposed techniques are cost effective and noninvasive, which are particularly advantageous for use in low-to-mid income countries because they reduce the financial burden and surgical risks caused by implantable devices. To achieve the long-term goals, the objectives of the current R21 proposal are to assess needs in Mexico, initiate preliminary studies and training, and plan, prepare, and assemble the information and data for a more comprehensive R01 submission. The team has made a preliminary assessment of the epilepsy research and medical needs in Mexico. Based on this pre-assessment, the following Specific Aims are designed to accomplish the proposal objectives: Aim 1 - Finalize the assessment of epilepsy research capacity and training needs in Mexico. Aim 2 - Develop multi-disciplinary collaboration to build Mexico research and clinical capacity in epilepsy. Aim 3 - Acquire preliminary data that will prepare the team for a follow-up R01 submission. Aim 4 - Integrate capacity building and collaborator training. Successful completion of the proposed research will change methods, treatments, and technologies in the field of epilepsy. This grant will help build sustainable research capacity in Mexico in epilepsy and neurological disorders in general. PUBLIC HEALTH RELEVANCE: For epilepsy control, successful demonstration of the effects of transcutaneous focal stimulation (TFS) will potentially change the current paradigms to noninvasive TFS for alternative or additive epilepsy therapy. For diagnosis, in the short-term, we expect the benefits of tripolar concentric ring electrodes (TCREs) to significantly improve the interpretability of EEG and, in the long-term, to advance epilepsy diagnosis.